Epithelial–mesenchymal transformation markers E-cadherin and survivin predict progression of stage pTa urothelial bladder carcinoma

Purpose

To determine whether the immunohistochemical markers survivin and E-cadherin can predict progress at initially diagnosed Ta bladder cancer.

Methods

We retrospectively searched for every initially diagnosed pTa urothelial bladder carcinoma having been treated at our single-center hospital in Germany from January 1992 up to December 2004. Follow-up was recorded up to June 2010, with recurrence or progress being the endpoints. Immunohistochemical staining and analysis of survivin and E-cadherin of the TURB specimens were performed. Outcome dependency of progression and no progression with immunohistochemical staining was analyzed using uni- and multivariate regression analysis, Kaplan–Meier analysis and uni- and multivariate Cox regression analysis.

Results

Overall, 233 patients were included. Forty-two percent of those were tumor free in their follow-up TURBs, 46 % had at least one pTa recurrence and 12 % even showed progress to at least pT1 bladder cancer. Aberrant staining of E-cadherin was found within 71 % of patients with progression in contrast to only 40 % in cases without progression (p = 0.004). Of all progressed patients, 92 % showed overexpression of survivin in their initial pTa specimen compared to 61 % without progression (p = 0.001). Kaplan–Meier analysis revealed aberrant E-cadherin staining to be associated with worse progression-free survival (PFS) (p = 0.005) as well as overexpression of survivin (p = 0.003). In multivariate Cox regression analysis, strong E-cadherin staining was an independent prognosticator for better PFS (p = 0.033) and multifocality (p = 0.046) and tumor size over 3 cm (p = 0.042) were prognosticators for worse PFS.

Conclusion

Adding the immunohistochemical markers survivin and E-cadherin could help to identify patients at risk of developing a progressive disease in initial stage pTa bladder cancer.

     

Lower body mass index and atrial fibrillation as independent predictors for mortality in patients with implantable cardioverter defibrillator

Aim

To evaluate risk factors related to total mortality in an unselected population of patients implanted with a cardioverter defibrillator.

Methods

Survival analysis was performed retrospectively investigating the records of 77 consecutive patients implanted with defibrillators (median 67 years, range 38-83 years; 63 men). All patients were followed regularly in 3-month intervals. The cause of mortality was assessed clinically, including post-mortem examination of device to assess possible arrhythmogenic death. Predictors were evaluated by Kaplan-Meier analysis with log-rank tests and by Cox regression analysis (proportional hazards).

Results

Defibrillator recipients had a mean (±SD) ejection fraction of 34 ± 13%, left ventricular end-diastolic dimension (LVEDD) of 6.24 ± 0.8 cm, QRS duration of 129 ± 34 ms, and body mass index (BMI) of 26.4 ± 4.3 kg/m². Atrial fibrillation was present in 32 patients, paroxysmal fibrillation in 23, and permanent fibrillation in 9 patients. The estimate of mean survival time for all patients was 51.5 (95% confidence interval 46.6-56.5) months. During the study period 11/77 (14%) patients died. Mean follow-up time was 24.5 months (range 0.2-60.7) for survivors and 7.6 months (range 1.5-42) for non-survivors. Independent predictors of mortality were the NYHA class (P = 0.004), BMI≤26 kg/m² (P = 0.024), presence of paroxysmal or permanent atrial fibrillation (P = 0.014), and absence of arterial hypertension (P = 0.010). LVEDD showed a weak significant effect on survival (P = 0.049).

Conclusion

Patients with implantable cardioverter defibrillator and a normal to lower BMI or atrial fibrillation had a significantly higher overall mortality. These factors may be indicative of end stage heart failure or diseases associated with high sympathetic activation.Patients with implantable cardioverter defibrillator, in addition to an intrinsic residual risk of sudden cardiac death due to a reduced effectiveness of defibrillators, have a high incidence of co-morbidities, which increase mortality in this population. Several studies have demonstrated that the implantation of a cardioverter defibrillator for both secondary and primary prevention significantly reduces total mortality by preventing sudden cardiac death (1-3). However, the death rate from non-arrhythmic causes among patients with implantable cardioverter defibrillator is substantial (4) and deserves further investigation. The purpose of this study was to investigate various risk factors with respect to total mortality in an unselected population of patients with implanted cardioverter defibrillator devices.     

Adipose tissue macrophages

It is now broadly accepted that low-grade chronic inflammation associated with obesity leads to the onset of insulin resistance and type 2 diabetes mellitus. Obesity-associated inflammation is characterized by an increased abundance of macrophages in adipose tissue along with production of inflammatory cytokines. Adipose tissue macrophages (ATMs) are suspected to be the major source of inflammatory mediators such as TNF-alpha and IL-6 that interfere with adipocyte function by inhibiting insulin action. However, ATMs phenotypically resemble alternatively activated (M2) macrophages and are capable of anti-inflammatory mediator production challenging the concept that ATMs are simply the "bad guys" in obese adipose tissue. Triggers promoting ATM recruitment, ATM functions and dysfunctions, and stimuli and molecular mechanisms that drive them into becoming detrimental to their environment are subject to current research. Strategies to interfere with ATM recruitment and adverse activation could give rise to novel options for treatment and prevention of insulin resistance and type 2 diabetes mellitus.     

Why do some trauma patients die while others survive? A matched-pair analysis based on data from Trauma Register DGU®

Purpose: The mortality rate for severely injured patients with the injury severity score (ISS) 16 has decreased in Germany. There is robust evidence that mortality is influenced not only by the acute trauma itself but also by physical health, age and sex. The aim of this study was to identify other possible influences on the mortality of severely injured patients. Methods: In a matched-pair analysis of data from Trauma Register DGU®, non-surviving patients from Germany between 2009 and 2014 with an ISS 16 were compared with surviving matching partners. Matching was performed on the basis of age, sex, physical health, injury pattern, trauma mechanism, conscious state at the scene of the accident based on the Glasgow coma scale, and the presence of shock on arrival at the emergency room. Results: We matched two homogeneous groups, each of which consisted of 657 patients (535 male, average age 37 years). There was no significant difference in the vital parameters at the scene of the accident, the length of the pre-hospital phase, the type of transport (ground or air), pre-hospital fluid management and amounts, ISS, initial care level, the length of the emergency room stay, the care received at night or from on-call personnel during the weekend, the use of abdominal sonographic imaging, the type of X-ray imaging used, and the percentage of patients who developed sepsis. We found a significant difference in the new injury severity score, the frequency of multi-organ failure, hemoglobine at admission, base excess and international normalized ratio in the emergency room, the type of accident (fall or road traffic accident), the pre-hospital intubation rate, reanimation, in-hospital fluid management, the frequency of transfusion, tomography (whole-body computed tomography), and the necessity of emergency intervention. Conclusion: Previously postulated factors such as the level of care and the length of the emergency room stay did not appear to have a significant influence in this study. Further studies should be conducted to analyse the identified factors with a view to optimising the treatment of severely injured patients. Our study shows that there are significant factors that can predict or influence the mortality of severely injured patients.     

Model predictive control of a collaborative manipulator considering dynamic obstacles

Collaborative robots have to adapt its motion plan to a dynamic environment and variation of task constraints. Currently, they detect collisions and interrupt or postpone their motion plan to prevent harm to humans or objects. The more advanced strategy proposed in this article uses online trajectory optimization to anticipate potential collisions, task variations, and to adapt the motion plan accordingly. The online trajectory planner pursues a model predictive control approach to account for dynamic motion objectives and constraints during task execution. The prediction model relates reference joint velocities to actual joint positions as an approximation of built-in robot tracking controllers. The optimal control problem is solved with direct collocation based on a hypergraph structure, which represents the nonlinear program and allows to efficiently adapt to structural changes in the optimization problem caused by moving obstacles. To demonstrate the effectiveness of the approach, the robot imitates pick-and-place tasks while avoiding self-collisions, semistatic, and dynamic obstacles, including a person. The analysis of the approach concerns computation time, constraint violations, and smoothness. It shows that after model identification, order reduction, and validation on the real robot, parallel integrators with compensation for input delays exhibit the best compromise between accuracy and computational complexity. The model predictive controller can successfully approach a moving target configuration without prior knowledge of the reference motion. The results show that pure hard constraints are not sufficient and lead to nonsmooth controls. In combination with soft constraints, which evaluate the proximity of obstacles, smooth and safe trajectories are planned.     

Prader-Willi syndrome

To complement the 2005 Annual Clinical Focus on medical genomics, AFP is publishing a series of short reviews on genetic syndromes. This series was designed to increase awareness of these diseases so that family physicians can recognize and diagnose children with these disorders and understand the type of care they might require in the future. This review discusses Prader-Willi syndrome.     

Olecranon fractures: factors influencing re-operation

Purpose

We evaluated factors influencing re-operation in tension band and plating of isolated olecranon fractures.

Methods

Four hundred eighty-nine patients with isolated olecranon fractures who underwent tension band (TB) or open reduction internal fixation (ORIF) from 2003 to 2013 were identified at an urban level 1 trauma centre. Medical records were reviewed for patient information and complications, including infection, nonunion, malunion, loss of function or hardware complication requiring an unplanned surgical intervention. Electronic radiographs of these patients were reviewed to identify Orthopaedic Trauma Association (OTA) fracture classification and patients who underwent TB or ORIF.

Results

One hundred seventy-seven patients met inclusion criteria of isolated olecranon fractures. TB was used for fixation in 43 patients and ORIF in 134. No statistical significance was found when comparing complication rates in open versus closed olecranon fractures. In a multivariate analysis, the key factor in outcome was method of fixation. Overall, there were higher rates of infection and hardware removal in the TB compared with the ORIF group.

Conclusions

Our results demonstrate that the dominant factor driving re-operation in isolated olecranon fractures is type of fixation. When controlling for all variables, there is an increased chance of re-operation in patients with TB fixation.